Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility

Rosadas, C. et al. (2022) Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility. Journal of Virological Methods, 302, 114475. (doi: 10.1016/j.jviromet.2022.114475) (PMID:35077719) (PMCID:PMC8782753)

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Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity. The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD). This class and species neutral assay showed a specificity of 100 % on 825 pre COVID-19 samples and a potential sensitivity of 99.6 % on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralization and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations. The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients.

Item Type:Articles
Additional Information:Janet T. Scott and Christopher Davis are members of the ISARIC4C Investigators. This work is variously supported by grants from: the National Institute for Health Research (NIHR; awardCO-CIN-01), theMedical Research Council (MRC; grantMC_PC_19059 andMC_PC_19078), MRC NIHR (grantCV220-111) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Wellcome Trust and Department for International Development (DID; 215091/Z/18/Z), theBill and Melinda Gates Foundation (OPP1209135), Liverpool Experimental Cancer Medicine Centre (grant reference C18616/ A25153), NIHR Biomedical Research Centre at Imperial College London (IS-BRC-1215-20013), EU Platform for European Preparedness Against (Re-) emerging Epidemics(PREPARE; FP7 project 602525), and NIHR Clinical Research Network for providing infrastructure support for this research. This work is supported by the Francis Crick Institute, which receives its core funding fromCancer Research UK (FC001061), the UK Medical Research Council (FC001061), and theWellcome Trust (FC001061).
Glasgow Author(s) Enlighten ID:Scott, Dr Janet and Davis, Dr Chris
Authors: Rosadas, C., Khan, M., Parker, E., Marchesin, F., Katsanovskaja, K., Sureda-Vives, M., Fernandez, N., Randell, P., Harvey, R., Lilley, A., Harris, B. H.L., Zuhair, M., Fertleman, M., Ijaz, S., Dicks, S., Short, C.-E., Quinlan, R., Taylor, G. P., Hu, K., McKay, P., Rosa, A., Roustan, C., Zuckerman, M., El Bouzidi, K., Cooke, G., Flower, B., Moshe, M., Elliott, P., Spencer, A. J., Lambe, T., Gilbert, S. C., Kingston, H., Baillie, J. K., Openshaw, P. J.M., Semple, M. G., Cherepanov, P., McClure, M. O., Tedder, R. S., ISARIC4C Investigators, , Scott, J. T., and Davis, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Virological Methods
ISSN (Online):1879-0984
Published Online:22 January 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Journal of Virological Methods 302: 114475
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
310665ISARIC - Coronavirus Clinical Characterisation ConsortiumAntonia HoMedical Research Council (MRC)MC_PC_19059 - 9815274III - Centre for Virus Research